Tissue engineering has been defined as an interdisciplinary field that applies the principles of engineering and life sciences toward the development of biological substitutes that restore, maintain, or improve tissue function. Three general strategies are employed in tissue engineering: use of isolated cells or cell substitutes, use of tissue-inducing substances, and use of cells placed on or within matrices.
Cells are often implanted or ‘seeded’ into an artificial structure capable of supporting three-dimensional tissue formation. These structures, typically called “scaffolds”, are often critical, both ex vivo as well as in vivo, to allowing cells to influence their own microenvironments. Scaffolds serve one or more of the following purposes: allow cell attachment and migration; deliver and retain cells and biochemical factors; enable diffusion of vital cell nutrients and expressed products; and exert certain mechanical and biological influences to modify the behavior of the cell phase.
To achieve the goal of tissue reconstruction, scaffolds must meet some specific requirements. A high porosity and an adequate pore size are necessary to facilitate cell seeding and diffusion throughout the whole structure of both cells and nutrients. A porous tissue scaffold (construct) should be sufficiently robust to accommodate the forces applied by cells and other outboard mechanical loads imposed during wound healing, blood flow, and patient activity. A scaffold's elastic properties are critical to its efficacy in regenerating tissue and reducing inflammatory responses, and must be matched with the elastic properties of native tissue. The elastic behavior of a porous scaffold can be described by its elastic modulus and Poisson's ratio, which depend on its porosity, the properties of the biomaterial making up the rib structures, and any anisotropic behavior due to the presence of pores. Optimizing these attributes requires control over pore size and geometry with the restriction of arranging the pores so they are open to the environment and completely interconnected.
Although yield strength and stiffness (elastic modulus) are of vital importance in providing the scaffold with satisfactory mechanical integrity, and show power-law behavior with regards to porosity, it does not fully characterize a construct's elastic behavior since it only describes deformation in the loading direction and does not address deformations in the transverse direction.
Poisson's ratio, on the other hand, describes the degree to which a material contracts (expands) transversally when axially strained, and is the property that addresses transverse strains resulting from axial deformations. The Poisson's ratio of virtually every porous biomaterial tissue construct is positive, i.e., it contracts in the transverse direction upon expanding in the axial direction. In some applications, scaffolds having a negative Poisson's ratio may be more suitable for emulating the behavior of native tissues and accommodating and transmitting forces to the host tissue site.
When Poisson's ratio is negative, expansion occurs in both the axial and transverse directions simultaneously. This unusual phenomenon has been show to occur in crystalline materials such as crystalline α-cristobalite SiO2, materials with hinged crystal structures, carbon allotropes, foams, microporous polymers and laminates, and other extreme states of matter. However, nothing has been reported on the fabrication of three-dimensional biomaterial constructs exhibiting a tunable negative Poisson's ratio.
It has been shown that man-made auxetic (negative Poisson's) polymers can be constructed by patterning non-auxetic polymers with an artificial lattice of rib-containing unit-cells (pores). Materials of this sort have been coined, cellular or hinged materials, owing to the fact that their constitutive pore structure can have a sizable effect on their mechanical behavior. Several unit-cell models have been proposed, each having well-defined strain-dependent Poisson's ratios (Poisson's function) described analytically. In the past, auxetic polyurethane foams have been formed by annealing the foams in a compressed state, which naturally causes a re-organization in their cellular microstructure. However, the annealing process renders little practical control over the cellular microstructure comprising the foams, making it very difficult to premeditatedly modulate the strain-dependent behavior of Poisson's ratio. In tissue engineering, one must have the capability to precisely tune the magnitude and polarity (positive or negative) of Poisson's ratio in three-dimensional constructs to match the properties of the specific tissue being regenerated. Moreover, such command over Poisson's ratio must also be attainable in biologically-relevant materials.
The elastic properties of a biomaterial tissue scaffold reflect its ability to handle external loading conditions and must be tailored to match the attributes of the underlying native tissue that it aims to repair. A scaffold's elastic modulus and Poisson's ratio describe how the biomaterial tissue scaffold supports and transmits external stresses to the host tissue site. While the elastic modulus is tunable in scaffolds, the Poisson's ratio of virtually every porous tissue construct is positive. The Poisson's ratio is positive/negative when the material contracts/expands transversally with axial expansion.